PMID- 34415762
OWN - NLM
STAT- MEDLINE
DCOM- 20211028
LR  - 20211028
IS  - 1535-3907 (Electronic)
IS  - 1535-3893 (Print)
IS  - 1535-3893 (Linking)
VI  - 20
IP  - 9
DP  - 2021 Sep 3
TI  - Allotype-Specific Glycosylation and Cellular Localization of Human Leukocyte 
      Antigen Class I Proteins.
PG  - 4518-4528
LID - 10.1021/acs.jproteome.1c00466 [doi]
AB  - Presentation of antigens by human leukocyte antigen (HLA) complexes at the cell 
      surface is a key process in the immune response. The alpha-chain, containing the 
      peptide-binding groove, is one of the most polymorphic proteins in the proteome. 
      All HLA class I alpha-chains carry a conserved N-glycosylation site, but little is 
      known about its nature and function. Here, we report an in-depth characterization 
      of N-glycosylation features of HLA class I molecules. We observe that different 
      HLA-A alpha-chains carry similar glycosylation, distinctly different from the HLA-B, 
      HLA-C, and HLA-F alpha-chains. Although HLA-A displays the broadest variety of glycan 
      characteristics, HLA-B alpha-chains carry mostly mature glycans, and HLA-C and HLA-F 
      alpha-chains carry predominantly high-mannose glycans. We expected these 
      glycosylation features to be directly linked to cellular localization of the HLA 
      complexes. Indeed, analyzing HLA class I complexes from crude plasma and inner 
      membrane-enriched fractions confirmed that most HLA-B complexes can be found at 
      the plasma membrane, while most HLA-C and HLA-F molecules reside in the 
      endoplasmic reticulum and Golgi membrane, and HLA-A molecules are more equally 
      distributed over these cellular compartments. This allotype-specific cellular 
      distribution of HLA molecules should be taken into account when analyzing peptide 
      antigen presentation by immunopeptidomics.
FAU - Hoek, Max
AU  - Hoek M
AD  - Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular 
      Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 
      Padualaan 8, Utrecht 3584 CH, The Netherlands.
AD  - Netherlands Proteomics Center, Padualaan 8, Utrecht 3584 CH, The Netherlands.
FAU - Demmers, Laura C
AU  - Demmers LC
AUID- ORCID: 0000-0002-6899-5484
AD  - Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular 
      Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 
      Padualaan 8, Utrecht 3584 CH, The Netherlands.
AD  - Netherlands Proteomics Center, Padualaan 8, Utrecht 3584 CH, The Netherlands.
FAU - Wu, Wei
AU  - Wu W
AUID- ORCID: 0000-0002-1092-603X
AD  - Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular 
      Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 
      Padualaan 8, Utrecht 3584 CH, The Netherlands.
AD  - Netherlands Proteomics Center, Padualaan 8, Utrecht 3584 CH, The Netherlands.
FAU - Heck, Albert J R
AU  - Heck AJR
AUID- ORCID: 0000-0002-2405-4404
AD  - Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular 
      Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 
      Padualaan 8, Utrecht 3584 CH, The Netherlands.
AD  - Netherlands Proteomics Center, Padualaan 8, Utrecht 3584 CH, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210820
PL  - United States
TA  - J Proteome Res
JT  - Journal of proteome research
JID - 101128775
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - *Antigen Presentation
MH  - Cell Membrane
MH  - Glycosylation
MH  - Golgi Apparatus
MH  - HLA Antigens
MH  - *Histocompatibility Antigens Class I
MH  - Histocompatibility Antigens Class II
MH  - Humans
PMC - PMC8419865
OTO - NOTNLM
OT  - cellular localization
OT  - glycobiology
OT  - glycoproteins
OT  - human leukocyte antigen (HLA)
OT  - major histocompatibility complex (MHC)
OT  - mass spectrometry (MS)
COIS- The authors declare no competing financial interest.
EDAT- 2021/08/21 06:00
MHDA- 2021/10/29 06:00
PMCR- 2021/09/06
CRDT- 2021/08/20 17:11
PHST- 2021/08/21 06:00 [pubmed]
PHST- 2021/10/29 06:00 [medline]
PHST- 2021/08/20 17:11 [entrez]
PHST- 2021/09/06 00:00 [pmc-release]
AID - 10.1021/acs.jproteome.1c00466 [doi]
PST - ppublish
SO  - J Proteome Res. 2021 Sep 3;20(9):4518-4528. doi: 10.1021/acs.jproteome.1c00466. 
      Epub 2021 Aug 20.